Abstract 095: CD74 Deficient Mice are Resistant to Toll-Like Receptor-Induced Preeclampsia Academic Article uri icon


  • Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by vascular endothelial dysfunction and excessive immunity and inflammation. Activation of the dsRNA receptor Toll-like receptor 3 (TLR3) or the ssRNA receptor TLR7 elicits a pregnancy-dependent PE-like syndrome in mice by inducing a pro-inflammatory immune response. CD74 (MHC Class II invariant chain) acts as a chaperone for MHC Class II surface expression on immune cells during antigen presentation and is cleaved into Class II-Associated Invariant Peptide (CLIP) following polyclonal activation of immune cell TLRs. The presence of CLIP in the groove of MHC Class II prevents T cell-dependent death leading to persistent immune cell activation. We hypothesized that genetic deletion of CD74 and subsequent depletion of CLIP on immune cells prevents TLR-induced immune responses and the development of PE in mice. Pregnant WT and CD74 KO mice were given i.p. injections of normal saline (P), poly I:C (TLR3 agonist; P-PIC), or R837 (TLR7 agonist; P-R837) on gestational days 13, 15, and 17 and euthanized on day 18. P-PIC and P-R837 WT mice had significantly increased splenic levels of pro-inflammatory CD3+/gd T cells and plasma levels of the gd T cell-derived cytokines IFNg, TNFa, and IL-17 compared to P WT mice whereas P-PIC and P-R837 CD74 KO mice had significantly increased anti-inflammatory CD3+/gd T cells and no significant increases in plasma IFNg, TNFa, and IL-17 levels. P-PIC and P-R837 CD74 KO mice did not develop the hypertension (gd17 SBP in mmHg: P WT=1023, P CD74 KO=1003, P-PIC WT=1474*, P-PIC CD74 KO=953, P-R837 WT=1332*, P-R837 CD74 KO=971; *p<0.05 vs. P WT), endothelial dysfunction, proteinuria, or placental necrosis seen in P-PIC and P-R837 WT mice. In conclusion, CD74 is crucial for the development of TLR-induced PE-like symptoms in mice and CD74/CLIP depletion may be a promising therapeutic target for women with PE.

published proceedings

  • Hypertension

author list (cited authors)

  • Hatahet, M., Gasheva, O. Y., Chiasson, V. L., Chatterjee, P., Bounds, K. R., Tobin, R. P., Newell-Rogers, M. K., & Mitchell, B. M.

citation count

  • 0

complete list of authors

  • Hatahet, Mohamad||Gasheva, Olga Y||Chiasson, Valorie L||Chatterjee, Piyali||Bounds, Kelsey R||Tobin, Richard P||Newell-Rogers, MK||Mitchell, Brett M

publication date

  • January 2014